Scholars@Duke
Paul Mitaari Magwene

Paul Mitaari Magwene

Professor of Biology
Biology
paul.magwene@duke.edu
Box 90338, Durham, NC 27708
124 Science Drive, Room 4103 FFSC, Duke Box 90338, Durham, NC 27708
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Selected Publications

Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis.

Journal Article PLoS Pathog · November 2023 The "Amoeboid Predator-Fungal Animal Virulence Hypothesis" posits that interactions with environmental phagocytes shape the evolution of virulence traits in fungal pathogens. In this hypothesis, selection to avoid predation by amoeba inadvertently selects ... Full text Link to item Cite

RNA viruses, M satellites, chromosomal killer genes, and killer/nonkiller phenotypes in the 100-genomes S. cerevisiae strains.

Journal Article G3 (Bethesda) · September 30, 2023 We characterized previously identified RNA viruses (L-A, L-BC, 20S, and 23S), L-A-dependent M satellites (M1, M2, M28, and Mlus), and M satellite-dependent killer phenotypes in the Saccharomyces cerevisiae 100-genomes genetic resource population. L-BC was ... Full text Link to item Cite

Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans.

Journal Article Proc Natl Acad Sci U S A · January 24, 2023 We recently reported transposon mutagenesis as a significant driver of spontaneous mutations in the human fungal pathogen Cryptococcus deneoformans during murine infection. Mutations caused by transposable element (TE) insertion into reporter genes were dr ... Full text Link to item Cite

Uncontrolled transposition following RNAi loss causes hypermutation and antifungal drug resistance in clinical isolates of Cryptococcus neoformans.

Journal Article Nat Microbiol · August 2022 Cryptococcus neoformans infections cause approximately 15% of AIDS-related deaths owing to a combination of limited antifungal therapies and drug resistance. A collection of clinical and environmental C. neoformans isolates were assayed for increased mutat ... Full text Link to item Cite

Epistatic genetic interactions govern morphogenesis during sexual reproduction and infection in a global human fungal pathogen.

Journal Article Proc Natl Acad Sci U S A · February 22, 2022 Cellular development is orchestrated by evolutionarily conserved signaling pathways, which are often pleiotropic and involve intra- and interpathway epistatic interactions that form intricate, complex regulatory networks. Cryptococcus species are a group o ... Full text Link to item Cite

Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review.

Journal Article J Fungi (Basel) · March 30, 2021 The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C. gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central ... Full text Link to item Cite

Pleiotropy and epistasis within and between signaling pathways defines the genetic architecture of fungal virulence.

Journal Article PLoS Genet · January 2021 Featured Publication Cryptococcal disease is estimated to affect nearly a quarter of a million people annually. Environmental isolates of Cryptococcus deneoformans, which make up 15 to 30% of clinical infections in temperate climates such as Europe, vary in their pathogenicity ... Full text Link to item Cite

Mitochondrial Genome Variation Affects Multiple Respiration and Nonrespiration Phenotypes in Saccharomyces cerevisiae.

Journal Article Genetics · February 2019 Mitochondrial genome variation and its effects on phenotypes have been widely analyzed in higher eukaryotes but less so in the model eukaryote Saccharomyces cerevisiae Here, we describe mitochondrial genome variation in 96 diverse S. cerevisiae strains and ... Full text Link to item Cite

Divergent Roles for cAMP-PKA Signaling in the Regulation of Filamentous Growth in Saccharomyces cerevisiae and Saccharomyces bayanus

Journal Article G3 (Bethesda, Md.) · November 2018 The cyclic AMP - Protein Kinase A (cAMP-PKA) pathway is an evolutionarily conserved eukaryotic signaling network that is essential for growth and development. In the fungi, cAMP-PKA signaling plays a critical role in regulating cellular physiology and morp ... Full text Open Access Cite

A High-Resolution Map of Meiotic Recombination in Cryptococcus deneoformans Demonstrates Decreased Recombination in Unisexual Reproduction.

Journal Article Genetics · June 2018 Multiple species within the basidiomycete genus Cryptococcus cause cryptococcal disease. These species are estimated to affect nearly a quarter of a million people leading to ∼180,000 mortalities, annually. Sexual reproduction, which can occur between hapl ... Full text Link to item Cite

Genetic Analysis of Complex Traits in Saccharomyces cerevisiae.

Journal Article Cold Spring Harbor protocols · June 2017 Defining the relationship between genotype and phenotype is a central challenge in biology. A powerful approach to this problem is to determine the genetic architecture and molecular basis of phenotypic differences among genetically diverse individuals. Full text Cite

Genetic Dissection of Heritable Traits in Yeast Using Bulk Segregant Analysis.

Journal Article Cold Spring Harbor protocols · June 2017 Bulk segregant analysis (BSA) is commonly used to determine the genetic basis of complex traits in yeast. This technique involves phenotyping progeny from a cross and then selectively genotyping pooled subsets of offspring with extreme phenotypes. Analysis ... Full text Cite

When sensing is gambling: An experimental system reveals how plasticity can generate tunable bet-hedging strategies.

Journal Article Evolution; international journal of organic evolution · April 2017 Genotypes can persist in unpredictable environments by "hedging their bets" and producing diverse phenotypes. Theoretical studies have shown that the phenotypic variability needed for a bet-hedging strategy can be generated by factors either inside or outs ... Full text Cite

Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains.

Journal Article Proceedings. Biological sciences · April 2017 Natural selection has the potential to act on all phenotypes, including genomic mutation rate. Classic evolutionary theory predicts that in asexual populations, mutator alleles, which cause high mutation rates, can fix due to linkage with beneficial mutati ... Full text Cite

The quick and the dead: microbial demography at the yeast thermal limit.

Journal Article Molecular ecology · March 2017 The niche of microorganisms is determined by where their populations can expand. Populations can fail to grow because of high death or low birth rates, but these are challenging to measure in microorganisms. We developed a novel technique that enables sing ... Full text Cite

Population perspectives on functional genomic variation in yeast.

Journal Article Briefings in functional genomics · March 2016 Advances in high-throughput sequencing have facilitated large-scale surveys of genomic variation in the budding yeast,Saccharomyces cerevisiae These surveys have revealed extensive sequence variation between yeast strains. However, much less is known about ... Full text Cite

Sporadic, Global Linkage Disequilibrium Between Unlinked Segregating Sites.

Journal Article Genetics · February 2016 Demographic, genetic, or stochastic factors can lead to perfect linkage disequilibrium (LD) between alleles at two loci without respect to the extent of their physical distance, a phenomenon that Lawrence et al. (2005a) refer to as "genetic indistinguishab ... Full text Cite

2μ plasmid in Saccharomyces species and in Saccharomyces cerevisiae.

Journal Article FEMS Yeast Res · December 2015 We determined that extrachromosomal 2μ plasmid was present in 67 of the Saccharomyces cerevisiae 100-genome strains; in addition to variation in the size and copy number of 2μ, we identified three distinct classes of 2μ. We identified 2μ presence/absence a ... Full text Link to item Cite

Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis.

Journal Article PLoS Pathog · November 2023 The "Amoeboid Predator-Fungal Animal Virulence Hypothesis" posits that interactions with environmental phagocytes shape the evolution of virulence traits in fungal pathogens. In this hypothesis, selection to avoid predation by amoeba inadvertently selects ... Full text Link to item Cite

RNA viruses, M satellites, chromosomal killer genes, and killer/nonkiller phenotypes in the 100-genomes S. cerevisiae strains.

Journal Article G3 (Bethesda) · September 30, 2023 We characterized previously identified RNA viruses (L-A, L-BC, 20S, and 23S), L-A-dependent M satellites (M1, M2, M28, and Mlus), and M satellite-dependent killer phenotypes in the Saccharomyces cerevisiae 100-genomes genetic resource population. L-BC was ... Full text Link to item Cite

Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans.

Journal Article Proc Natl Acad Sci U S A · January 24, 2023 We recently reported transposon mutagenesis as a significant driver of spontaneous mutations in the human fungal pathogen Cryptococcus deneoformans during murine infection. Mutations caused by transposable element (TE) insertion into reporter genes were dr ... Full text Link to item Cite

Uncontrolled transposition following RNAi loss causes hypermutation and antifungal drug resistance in clinical isolates of Cryptococcus neoformans.

Journal Article Nat Microbiol · August 2022 Cryptococcus neoformans infections cause approximately 15% of AIDS-related deaths owing to a combination of limited antifungal therapies and drug resistance. A collection of clinical and environmental C. neoformans isolates were assayed for increased mutat ... Full text Link to item Cite

Epistatic genetic interactions govern morphogenesis during sexual reproduction and infection in a global human fungal pathogen.

Journal Article Proc Natl Acad Sci U S A · February 22, 2022 Cellular development is orchestrated by evolutionarily conserved signaling pathways, which are often pleiotropic and involve intra- and interpathway epistatic interactions that form intricate, complex regulatory networks. Cryptococcus species are a group o ... Full text Link to item Cite

Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review.

Journal Article J Fungi (Basel) · March 30, 2021 The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C. gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central ... Full text Link to item Cite

Pleiotropy and epistasis within and between signaling pathways defines the genetic architecture of fungal virulence.

Journal Article PLoS Genet · January 2021 Featured Publication Cryptococcal disease is estimated to affect nearly a quarter of a million people annually. Environmental isolates of Cryptococcus deneoformans, which make up 15 to 30% of clinical infections in temperate climates such as Europe, vary in their pathogenicity ... Full text Link to item Cite

Mitochondrial Genome Variation Affects Multiple Respiration and Nonrespiration Phenotypes in Saccharomyces cerevisiae.

Journal Article Genetics · February 2019 Mitochondrial genome variation and its effects on phenotypes have been widely analyzed in higher eukaryotes but less so in the model eukaryote Saccharomyces cerevisiae Here, we describe mitochondrial genome variation in 96 diverse S. cerevisiae strains and ... Full text Link to item Cite

Divergent Roles for cAMP-PKA Signaling in the Regulation of Filamentous Growth in Saccharomyces cerevisiae and Saccharomyces bayanus

Journal Article G3 (Bethesda, Md.) · November 2018 The cyclic AMP - Protein Kinase A (cAMP-PKA) pathway is an evolutionarily conserved eukaryotic signaling network that is essential for growth and development. In the fungi, cAMP-PKA signaling plays a critical role in regulating cellular physiology and morp ... Full text Open Access Cite

A High-Resolution Map of Meiotic Recombination in Cryptococcus deneoformans Demonstrates Decreased Recombination in Unisexual Reproduction.

Journal Article Genetics · June 2018 Multiple species within the basidiomycete genus Cryptococcus cause cryptococcal disease. These species are estimated to affect nearly a quarter of a million people leading to ∼180,000 mortalities, annually. Sexual reproduction, which can occur between hapl ... Full text Link to item Cite

Genetic Analysis of Complex Traits in Saccharomyces cerevisiae.

Journal Article Cold Spring Harbor protocols · June 2017 Defining the relationship between genotype and phenotype is a central challenge in biology. A powerful approach to this problem is to determine the genetic architecture and molecular basis of phenotypic differences among genetically diverse individuals. Full text Cite

Genetic Dissection of Heritable Traits in Yeast Using Bulk Segregant Analysis.

Journal Article Cold Spring Harbor protocols · June 2017 Bulk segregant analysis (BSA) is commonly used to determine the genetic basis of complex traits in yeast. This technique involves phenotyping progeny from a cross and then selectively genotyping pooled subsets of offspring with extreme phenotypes. Analysis ... Full text Cite

When sensing is gambling: An experimental system reveals how plasticity can generate tunable bet-hedging strategies.

Journal Article Evolution; international journal of organic evolution · April 2017 Genotypes can persist in unpredictable environments by "hedging their bets" and producing diverse phenotypes. Theoretical studies have shown that the phenotypic variability needed for a bet-hedging strategy can be generated by factors either inside or outs ... Full text Cite

Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains.

Journal Article Proceedings. Biological sciences · April 2017 Natural selection has the potential to act on all phenotypes, including genomic mutation rate. Classic evolutionary theory predicts that in asexual populations, mutator alleles, which cause high mutation rates, can fix due to linkage with beneficial mutati ... Full text Cite

The quick and the dead: microbial demography at the yeast thermal limit.

Journal Article Molecular ecology · March 2017 The niche of microorganisms is determined by where their populations can expand. Populations can fail to grow because of high death or low birth rates, but these are challenging to measure in microorganisms. We developed a novel technique that enables sing ... Full text Cite

Population perspectives on functional genomic variation in yeast.

Journal Article Briefings in functional genomics · March 2016 Advances in high-throughput sequencing have facilitated large-scale surveys of genomic variation in the budding yeast,Saccharomyces cerevisiae These surveys have revealed extensive sequence variation between yeast strains. However, much less is known about ... Full text Cite

Sporadic, Global Linkage Disequilibrium Between Unlinked Segregating Sites.

Journal Article Genetics · February 2016 Demographic, genetic, or stochastic factors can lead to perfect linkage disequilibrium (LD) between alleles at two loci without respect to the extent of their physical distance, a phenomenon that Lawrence et al. (2005a) refer to as "genetic indistinguishab ... Full text Cite

2μ plasmid in Saccharomyces species and in Saccharomyces cerevisiae.

Journal Article FEMS Yeast Res · December 2015 We determined that extrachromosomal 2μ plasmid was present in 67 of the Saccharomyces cerevisiae 100-genome strains; in addition to variation in the size and copy number of 2μ, we identified three distinct classes of 2μ. We identified 2μ presence/absence a ... Full text Link to item Cite

The 100-genomes strains, an S. cerevisiae resource that illuminates its natural phenotypic and genotypic variation and emergence as an opportunistic pathogen.

Journal Article Genome Res · May 2015 Featured Publication Saccharomyces cerevisiae, a well-established model for species as diverse as humans and pathogenic fungi, is more recently a model for population and quantitative genetics. S. cerevisiae is found in multiple environments-one of which is the human body-as a ... Full text Link to item Cite

Revisiting mortimer's genome renewal hypothesis: Heterozygosity, homothallism, and the potential for adaptation in yeast

Journal Article Advances in Experimental Medicine and Biology · January 1, 2014 In diploid organisms, the frequency and nature of sexual cycles have a major impact on genome-wide patterns of heterozygosity. Recent population genomic surveys in the budding yeast, Saccharomyces cerevisiae, have revealed surprising levels of genomic hete ... Full text Cite

Biomechanics of turtle shells: how whole shells fail in compression.

Journal Article Journal of experimental zoology. Part A, Ecological genetics and physiology · February 2013 Turtle shells are a form of armor that provides varying degrees of protection against predation. Although this function of the shell as armor is widely appreciated, the mechanical limits of protection and the modes of failure when subjected to breaking str ... Full text Cite

The genetic architecture of biofilm formation in a clinical isolate of Saccharomyces cerevisiae.

Journal Article Genetics · February 2013 Featured Publication Biofilms are microbial communities that form on surfaces. They are the primary form of microbial growth in nature and can have detrimental impacts on human health. Some strains of the budding yeast Saccharomyces cerevisiae form colony biofilms, and there i ... Full text Link to item Cite

Pleiotropic signaling pathways orchestrate yeast development.

Journal Article Curr Opin Microbiol · December 2011 Developmental phenotypes in Saccharomyces cerevisiae and related yeasts include responses such as filamentous growth, sporulation, and the formation of biofilms and complex colonies. These developmental phenotypes are regulated by evolutionarily conserved, ... Full text Link to item Cite

The statistics of bulk segregant analysis using next generation sequencing.

Journal Article PLoS Comput Biol · November 2011 Featured Publication We describe a statistical framework for QTL mapping using bulk segregant analysis (BSA) based on high throughput, short-read sequencing. Our proposed approach is based on a smoothed version of the standard G statistic, and takes into account variation in a ... Full text Link to item Cite

Natural variation in CDC28 underlies morphological phenotypes in an environmental yeast isolate.

Journal Article Genetics · July 2011 Morphological differences among individuals in a species represent one of the most striking aspects of biology, and a primary aim of modern genetics is to uncover the molecular basis of morphological variation. In a survey of meiosis phenotypes among envir ... Full text Cite

Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae.

Journal Article Proc Natl Acad Sci U S A · February 1, 2011 Featured Publication We carried out a population genomic survey of Saccharomyces cerevisiae diploid isolates and find that many budding yeast strains have high levels of genomic heterozygosity, much of which is likely due to outcrossing. We demonstrate that variation in hetero ... Full text Link to item Cite

Environmental and genetic determinants of colony morphology in yeast.

Journal Article PLoS Genet · January 22, 2010 Featured Publication Nutrient stresses trigger a variety of developmental switches in the budding yeast Saccharomyces cerevisiae. One of the least understood of such responses is the development of complex colony morphology, characterized by intricate, organized, and strain-sp ... Full text Open Access Link to item Cite

Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal.

Journal Article Genes Dev · November 1, 2009 Despite the identification of some key genes that regulate sex determination, most cases of disorders of sexual development remain unexplained. Evidence suggests that the sexual fate decision in the developing gonad depends on a complex network of interact ... Full text Link to item Cite

Using correlation proximity graphs to study phenotypic integration

Journal Article Evolutionary Biology · September 1, 2008 Characterizing and comparing the covariance or correlation structure of phenotypic traits lies at the heart of studies concerned with multivariate evolution. I describe an approach that represents the geometric structure of a correlation matrix as a type o ... Full text Cite

Integration and modularity in biological systems: A review

Journal Article Acta Zoologica Sinica · 2006 Cite

Computational challenges for integrative genomics

Journal Article Genomics and Informatics · 2004 Cite

Estimating genomic coexpression networks using first-order conditional independence.

Journal Article Genome Biol · 2004 Featured Publication We describe a computationally efficient statistical framework for estimating networks of coexpressed genes. This framework exploits first-order conditional independence relationships among gene-expression measurements to estimate patterns of association. W ... Full text Link to item Cite

Reconstructing the temporal ordering of biological samples using microarray data.

Journal Article Bioinformatics · May 1, 2003 Featured Publication MOTIVATION: Accurate time series for biological processes are difficult to estimate due to problems of synchronization, temporal sampling and rate heterogeneity. Methods are needed that can utilize multi-dimensional data, such as those resulting from DNA m ... Full text Link to item Cite

The naturalist in a world of genomics.

Journal Article The American naturalist · February 2003 Functional genomics provides new opportunities to address issues of fundamental interest in evolutionary biology and suggests many new research directions that are ripe for evolutionary investigation. New types of data, and the ability to study biological ... Full text Cite

New tools for studying integration and modularity.

Journal Article Evolution · September 2001 Featured Publication The study of phenotypic integration concerns the modular nature of organismal phenotypes. The concept provides a rationale for why certain subsets of phenotypic traits show particularly high levels of association over development and/or evolution. The tech ... Full text Link to item Cite

Comparing ontogenetic trajectories using growth process data.

Journal Article Systematic biology · September 2001 Ontogenetic trajectories are commonly quantified by characterizing changes in the sizes and shapes of organisms over the course of development. This formulation of ontogenetic transformations can be misleading in that it ignores critical aspects of the bio ... Full text Cite

Predatory Dinosaurs from the Sahara and Late Cretaceous Faunal Differentiation

Journal Article Science (New York, N.Y.) · May 1996 Late Cretaceous (Cenomanian) fossils discovered in the Kem Kem region of Morocco include large predatory dinosaurs that inhabited Africa as it drifted into geographic isolation. One, represented by a skull approximately 1.6 meters in length, is an advanced ... Full text Cite